CXCL13及其受体 CXCR5与结直肠癌转移及 KRAS 基因突变关系的探讨

摘要

Objective To observe the expression of chemotactic factor CXCR5-CXCL13 in the metastasis lymphono-dus of colorectal carcinoma, and explore the correlation between the expression of CXCR5-CXCL13 and colorectal carcino-ma metastasis and the mutation of KRAS gene.Methods The immunohistochemistry staining method was used to detect the protein expression of CXCR5-CXCL13 in 148 specimens of colorectal cancer and lymphonodus metastasis tissues and to-gether with 95 control samples.The Real-time Polymerase Chain Reaction ( Realtime-PCR) technique was used to examine the mutations of KRAS gene in 148 specimens.We analysis the correlation between expression of CXCR5-CXCL13 and clinical pathological parameters, survival data and KRAS mutation.Results CXCR5 was mainly expressed in epithelial cell while CXCL13 was mostly found in interstitial cell.The protein levels of CXCR5-CXCL13 in colorectal cancer were up-regulated than normal tissues (P<0.05), and also higher in metastasis lymphaden than normal ones (P<0.05).The protein levels of CXCR5 and CXCL13 in colorectal cancer and metastasis lymphaden correlated positively ( P<0.05 ) . Conclusions CXCR5-CXCL13 may play an important role in development, metastasis and relapse of colon cancer, and which can be used as a prognostic marker of colorectal carcinoma.CXCR5-CXCL13 expressing and KRAS mutation turn up at the same time, which may imply they interactive with each other.The research of CXCR5-CXCL13 may offer a new drug-target for the anti-colorectal carcinoma.%目的：观察趋化因子CXCL13及其受体CXCR5在结直肠癌转移灶中的表达变化，探讨其与结直肠癌转移及KRAS基因突变的关系。方法选择97例结直肠癌组织标本（观察A组）、51例淋巴结转移灶标本（观察B组），同时选择52例正常结直肠标本（对照A组）和43例正常淋巴结标本（对照B组）。用免疫组织化学法检测CXCL13及CXCR5蛋白在上述组织中的表达，分析其与临床病理参数、患者生存时间之间的关系。用Real Time PCR法检测148例结直肠癌组织KRAS基因突变情况，并分析其与CXCL13及CXCR5蛋白表达的关系。结果CXCR5在上皮细胞的表达率较高，CXCL13在间质细胞的表达较高。 CXCL13及其受体CXCR5蛋白在结直肠癌组织的表达高于正常组织（P＜0．05），在转移淋巴结中的表达明显高于正常淋巴结（P＜0．05）。在结直肠癌原发灶和淋巴结转移灶中，CXCL13及其受体CXCR5蛋白的表达均具有明显的相关性（P＜0．05）。在CXCL13及其受体CXCR5表达的患者中，其中位生存时间明显短于其阴性表达者（ P均＜0．05）。观察A组KRAS基因突变型36例（其中CXCL13表达阳性12例、CXCR5表达阳性17例），野生型61例（其中CXCL13表达阳性23例、CXCR5表达阳性23例），CXCL13及CXCR5蛋白表达与KRAS基因是否发生突变均有相关性（P均＜0．05）。观察B组KRAS基因突变型20例（其中CXCL13表达阳性16例、CXCR5表达阳性14例），野生型31例（其中CXCL13表达阳性8例、CXCR5表达阳性11例），CXCL13及CXCR5蛋白表达与KRAS基因是否发生突变均有相关性（P均＜0．05）。结论趋化因子CXCL13及其受体CXCR5蛋白在结直肠组织淋巴细胞的归巢及结直肠癌淋巴结的转移中发挥重要的作用，对预测结直肠癌的转移及评估预后有一定的价值。 CXCL13及CXCR5蛋白表达与KRAS基因突变具有较高的一致性。